There are more than 80 autoimmune diseases and the most common include type 1 diabetes, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus. While the exact causes of many autoimmune diseases remain largely unknown, experts tend to agree that genes – together with infections and other environmental factors – play an important role. A recent review of published evidence finds that global rates of autoimmune diseases have increased considerably over the past 30 years, particularly in industrialized nations. The National Institutes of Health (NIH) estimates suggest that there are more than 23 million people in the United States living with a condition of autoimmunity. Many treatments involve taking medications for patients who suppress the immune system, so that it does not react in an exaggerated manner. However, such a general approach implies that the immune system is being debilitated to deal with other diseases.
Researchers are therefore looking for ways to intervene only in that part of the immune system that reacts erroneously to the particular disease. For the new study, a team from the Whitehead Institute for Biomedical Research in Cambridge sought to improve a technique called “tolerance induction”, which sounds good in theory, but is proving difficult to apply. The principle of tolerance induction consists in using antigenic peptides or protein fragments from particular cells that the immune system is exaggerating and retraining the immune system to ignore. However, scientists are finding the idea difficult to put into practice. For example, a particular obstacle lies in bringing the antigenic peptides to reach their destination before the immune cells destroy them. To remedy this, the team behind the new study decided to try a method that uses red blood cells to transport the antigenic peptides.
The red blood cells (erythrocytes) would be particularly suitable for transporting the specific antigen of the disease because, by bringing oxygen to the cells, they can reach practically every part of the body. Another reason is that red blood cells are recycled frequently – every month in mice and every 4 months in humans – without eliciting an immune system response. For the new study, the researchers built on previous work in which they had attached a chemical tag and antibodies to red blood cells using a method that they called “sortage”. They used sortagging to attack the antigens that activate the specific immune response of red blood cell disease from mice with multiple sclerosis and type 1 diabetes, and then transfused them into mice again. The whole procedure took about 1 hour. The results showed that the mice had reduced the symptoms of the disease and also a transfusion before the developed disease was sufficient to reduce the symptoms, the researchers note.
Explains the first author Novalia Pishesha: “Basically what we are doing, is redirecting the way of red blood cell clearance, so that the foreign antigen masks like red blood cells, so that these antigens are tolerated in the process. while our results suggest that the use of red blood cells to carry antigenic peptides seems to be an effective way to induce immune tolerance, the underlying molecular and cellular mechanisms are unclear. This study surely provides a good starting point for further research on how the immune system self-regulates and because sometimes it does the wrong thing. New treatments that prevent and alleviate autoimmune diseases can come from the use of red blood cells, to transport specific proteins of the disease that re-qualify the immune system. we will do a study that shows if such an approach works in mice with multiple sclerosis and type 1 diabetes.
Due to the importance of the implications, the study was published in the prestigious PNAS magazine.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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